We have recently completed a study to evaluate the safety and efficacy of passive immunization with a human hyperimmune globulin (BPIG) in preventing Haemophilus influenzae (HI) and other infections. BPIG is prepared from the pooled plasma of adult donors immunized with Hib, pneumococcal and meningococcal vaccines. Between June 1983 and April 1986, infants were randomized in a double-blind fashion to receive BPIG (n=353) or placebo (n=350) at 2, 6 and 10 months of age. Between the receipt of the first BPIG/placebo injection at 2 months of age and age 14 months, which is 4 months after receiving the third and final BPIG/placebo injection, 8 infants had invasive Hib disease (3 meningitis and 5 bacteremia). Seven of these were in the placebo group and only 1 was in the BPIG group (p=0,034). There was also a suggestion that BPIG may protect against pneumococcal infections. There were not sufficient number of cases however, to draw firm conclusions, since majority of pneumococcal infections occurred in the second year of life (after BPIG/placebo were discontinued). In the proposed trial we will extend these studies to examine the efficacy of BPIG in preventing pneumococcal infections and the biology of pneumococcal colonization and infection. In order to fully evaluate the mechanisms of protection and the effects of BPIG on the development immune system, we will compare in placebo and BPIG on the development immune system, we will compare in placebo and BPIG treated infants (a) the rates of acquisition and duration of carriage of type specific pneumococcus in the oropharynx (OP) (b) serum type specific antibody responses to OP colonization and to invasive pneumococcal disease, (c) the rate of acquisition of "natural" antibody to different serotypes of pneumococcus. We will also compare the ability of Apache and Caucasians of various ages to make an antibody response to bacterial polysaccharide vaccines and search for immunogenetic markers that might predict individuals with poor antibody responses and high risk of infection.